tbuckley/cabot-search huggingface dataset:
Abstract 11211: Kawasaki Disease Like Vasculitis Facilitate Atherosclerosis and Statin Shows Significant Antiatherosclerosis and Antiinflammatory Effect in Kawasaki Disease Model Mouse
Authors: Yusuke Motoji, Ryuji Fukazawa, Miyagi Yasuo, Yasuhiko Itoh, Yosuke Ishii
Journal: Circulation (2022)

Introduction: Kawasaki disease (KD) is an acute form of systemic vasculitis that may promote atherosclerosis in adulthood. We reported last year that CAWS vasculitis, a KD-like vasculitis, induces atherosclerosis in ApoE -/- mice and that statin suppress atherosclerosis and vasculitis. For further validation, we focused on macrophage cells and its fractionations. Hypothesis: Statins have a therapeutic effect by affecting the macrophage cell infiltration and fractionation. Methods: CAWS was injected intraperitoneally in 5-week-old male ApoE-/- mice, and they were divided into 4 groups: the control, CAWS, CAWS+statin, and Late-statin groups. They were sacrificed at 6 or 10 weeks after CAWS injection and blood samples, aorta and heart were taken. Statin was started after CAWS injection, except for the late-statin group, which was administrated statin internally 6 weeks after injection. The serum was assayed for LDL/VLDL cholesterol. The aortic root and abdominal aorta were evaluated with HE staining and immunostaining (Macrophage fractionation; M1+M2(anti-Mac2), M1 (anti-CD80), M2 (anti-CD206)). Results: These serum LDL/VLDL cholesterol levels were elevated in all groups. CAWS significantly accumulated inflammatory cells, including macrophage cells, in both the aorta and abdominal aorta(Macrophage at aortic root: 6wks; Control 0.34±0.08% vs. CAWS 10.22±2.17 (p=0.030), 10wks; 0.67±0.39 vs. 6.48±1.07 (p=0.052)).Statins significantly inhibited macrophage cell infiltration at the aortic root. The M2/M1 ratio was significantly increased in the statin group(6wks; CAWS 0.10±0.05% vs. CAWS+statin 1.10±0.27 (p=0.030), 10wks; 0.17±0.10 vs. 0.96±0.15 (p=0.030)). The Late-statin group was also found to have about the same above therapeutic effects. Conclusions: It was suggested that statins might suppress CAWS vasculitis and atherosclerosis by inhibiting the accumulation or differentiation of macrophage cells (mainly M1) and increasing M2 cells, which have tissue repair effects. Statin was effective for prevention of atherosclerosis even when in the late phase. In the future, this study would be expected to contribute to expanding the indications of statin therapy for patients with KD who have cardiovascular sequelae.
Abstract 12469: Ras-Related Associated With Diabetes (RRAD) Regulates Cardiomyocyte Response to Cell Cycle Stimulation
Authors: Riham Abouleisa, Abou bakr M Salama, Jessica Miller, Fareeha Abdulwali, dana Hammouri, Qinghui Ou, douglas andres, Jonathan Satin, Bradford G Hill, Tamer Mohamed
Journal: Circulation (2022)

Background: Cardiomyocytes (CMs) lost during ischemic cardiac injury can't be replaced due to their limited proliferative capacity. Our laboratory has shown that overexpression of cyclin-dependent kinase 1 (CDK1), CDK4, cyclin B1, and cyclin D1 in combination (4F) promotes cell division in 10-20% of post-mitotic cardiomyocytes (CMs). Recently, we found that 4F overexpression transiently decreased CM contractility during the mitotic phase. Temporal bulk and single-cell RNAseq data from 4F-transduced human iPSC-derived CMs (hiPS-CMs) or P7 neonatal mouse CMs (NMCM) indicated a transient downregulation of contractile genes during the mitotic phase; among the most differentially regulated genes was Ras-Related Associated with Diabetes (RRAD), an endogenous inhibitor of the L-type calcium channel (LTCC). Objective: RRAD inhibition of LTCC primes CMs to respond to cell cycle stimulation through unloading CMs from their commitment to contractile function. Methods and Results: We used viral approaches to overexpress and knockdown (KD) RRAD in hiPS-CMs and NMCM. Functionally, RRAD overexpression abolished intracellular calcium transients’ amplitude while RRAD KD significantly increased calcium transients’ amplitude in response to electric stimulation in CMs. RRAD overexpression in hiPS-CMs or P7 NMCM augments the cell cycle induction following 4F transduction, while RRAD KD resulted in a decline in the cell cycle induction as indicated by cell cycle markers; EDU and PHH3 (PHH3(%): 4F 26.0± 1, 4F+RRAD 41.15± 6.7, 4F+KD 15.92± 2.6, P&lt;0.05; EDU(%): 4F 29.9± 3.9, 4F+RRAD 61.04± 2.6, 4F+KD 16.8± 2.8; n=6, P&lt;0.05). Nitrendipine, an LTCC blocker, and Mavacamten, which directly suppress cardiomyocyte contractility, reversed the inhibitory effect of RRAD KD on cell cycle induction. More interestingly, RRAD overexpression enhanced the cell cycle induction in presence of only 2 factors (CDK4 and CCND (2F)), which are known to induce S phase (PHH3(%): 2F 5.1± 0.4, 2F+RRAD 10.4± 6.7, 2F+KD 0.4± 0.1, EDU (%); 2F 38.6±15, 2F +RRAD 44.7± 18, 2F+KD 5.6± 2; n=6, P&lt;0.05). Conclusions: These data suggest that RRAD modulation of contractile function modulates the response of CMs to cell cycle induction and can reduce the number of factors needed to induce cell cycle in CMs.
Abstract 12596: Comparison of the Efficacy and Safety of Direct Oral Anticoagulants With Vitamin K Antagonists in Patients With Thrombotic Antiphospholipid Syndrome: Systematic Review and Meta-analysis of Randomized Clinical Trials
Authors: Antoine Bejjani, Candrika D Khairani, Gregory Piazza, David Jimenez, Manuel Monreal, Saurav Chatterjee, Vittorio Pengo, Scott Woller, Josefina Cortes-Hernandez, Jean M Connors, Yogendra Kanthi, Harlan M Krumholz, Saskia Middeldorp, Anna Falanga, Mary Cushman, Samuel Z Goldhaber, David Garcia, Behnood Bikdeli
Journal: Circulation (2022)

Introduction: The efficacy and safety of direct oral anticoagulants (DOACs) as treatment alternatives for patients with thrombotic antiphospholipid syndrome (APS) remain controversial. Methods: We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) that compared the efficacy and safety of DOACs with vitamin-K antagonists (VKAs) in patients with thrombotic APS. We searched PubMed, EMBASE and Cochrane Central Register of Controlled Trials through April 9, 2022. Main efficacy outcomes were a composite of arterial thrombotic events, and a composite of venous thromboembolic events (VTE). The main safety outcome was major bleeding according to the International Society on Thrombosis and Hemostasis (ISTH) criteria. A random effects model with inverse variance was used for the primary analysis. Risk of bias was assessed using the Cochrane Collaboration criteria. Results: Our search retrieved 253 studies. Four RCTs involving 474 patients were included (Figure). All four RCTs were open-label but had proper random sequence generation and adequate allocation concealment. The DOACs used were rivaroxaban (3 trials) and apixaban (1 trial). The mean percent time in therapeutic range in the warfarin arm among the four studies was 60%. Overall, use of DOACs compared with VKAs was associated with increased odds of composite of arterial thrombotic events (OR 5.64, 95% confidence interval [CI] 1.96-16.27, p =0.001, I 2 = 0%). The odds of subsequent VTE events (OR 1.19, 95% CI 0.31-4.53, p =0.80, I 2 = 0%), or major bleeding (OR 1.02, 95% CI 0.42-2.47, p =0.97, I 2 = 0%) were not significantly different between the two groups. Conclusions: Patients with thrombotic APS randomized to DOACs compared to VKAs appear to have increased risk for arterial thrombosis. No significant differences were observed between patients randomized to DOACs vs VKAs in the risk of subsequent VTE or major bleeding.
Abstract 12348: High-Risk Low-Density Non-Calcified Plaque Morphology
Authors: Shant Malkasian, Tami Crabtree, Sabee Molloi, Hugo Marques, James K Min, Hyuk-Jae Chang, Andrew Choi, James Earls
Journal: Circulation (2022)

Hypothesis The morphology of low-density non-calcified coronary plaque is associated with acute coronary syndrome (ACS) and culprit lesion precursors Methods: This was a post-hoc analysis of the multicenter ICONIC study. A subset of 94 patients suspected of coronary artery disease (CAD) underwent coronary CT angiography imaging (CCTA) with subsequent follow-up for the occurrence of the first ACS event were selected. At the time of ACS, the culprit lesion was adjudicated by invasive coronary angiography cardiologists blinded to the CCTA. Quantitative CT was performed by a validated software as a service (Cleerly Labs, Cleerly, Inc., Denver, CO). A level-III reader used multiplanar reformation (MPR) images from this analysis to qualitatively assess individual collections of low-density non-calcified (LDNC) plaques (-189 to 30 HU). The degree of embedded LDNC plaque (DELP) was the amount a LDNC plaque was surrounded by non-calcified plaque. DELP was categorized as 90, 180, 270, and 360. LDNC plaque shape was categorized as crescent, round, lobular, or bean-shaped. DELP and shape were qualitatively assessed using the cross-sectional MPR image with the greatest LDNC plaque area. LDNC plaques with &gt;270 DELP and round or bean-shaped were considered high-risk plaque (HRP) morphology. Results: ACS occurred in 64 patients. 247 LDNC plaques were analyzed. Patients without and with ACS had, on average 0.40±0.86 and 1.02±1.21 (p-value = 0.014) LDNC plaques with HRP morphology. The proportional hazard ratio associating the presence of one or more HRP morphology plaques with ACS was 2.03 (1.19, 3.48; p-value = 0.009), after controlling for diameter stenosis, age, sex, and family history of CAD. The odds ratio of the association of HRP morphology with culprit lesion precursors was 10.93 (3.77, 31.71; p-value &lt;0.001), after controlling for diameter stenosis, age, sex, and family history of CAD. Conclusion HRP morphology may improve the stratification of patients at risk for ACS.
Abstract 12418: Prevalence and Clinical Characteristics of Patients With Decompensated Heart Failure and Clonal Haematopoiesis of Indeterminate Potential
Authors: Leanne Mooney, Neil A Robertson, Maria T Terradas, Carl S Goodyear, Mhairi Copland, John J McMurray, Kristina Kirschner, Chandra Tamir, Mark Petrie, Ninian Lang
Journal: Circulation (2022)

Introduction: CHIP is associated with inflammation, atherogenesis and poor outcomes in patients with HFrEF. Although inflammation may be important in the pathophysiology of HFpEF, CHIP has not previously been assessed in patients with HFpEF. We examined the prevalence of CHIP and its associated clinical characteristics in patients with HFpEF or HFrEF. Methods: Error-corrected targeting sequencing of 75 known haematopoietic driver genes was performed on peripheral blood DNA from patients admitted to hospital with acute HF (HFrEF [LVEF&lt;40%] and HFpEF [LVEF≥40%]). CHIP mutations and their associated clonal population size were analysed and associations with clinical phenotypes and inflammatory markers were assessed. Results: 96 patients were enrolled; 48 had HFrEF and 48 had HFpEF. CHIP mutations with VAF ≥2% were detected in 5 patients with HFrEF (10%) and 8 patients with HFpEF (17%). CHIP mutations with VAF ≥1% were detected in 25 patients with HFrEF (52%) and 21 patients with HFpEF (44%). HFrEF patients with CHIP were a similar age to those without CHIP (71.1 ± 14.2yrs CHIP vs 68.9 ± 13.0yrs without CHIP; p=0.58) but HFpEF patients with CHIP were older than those without CHIP (80.1 ± 8.8yrs CHIP vs 70.0 ± 12.3yrs no CHIP; p=0.002). There was an age-dependent rise in CHIP prevalence which appeared greater in patients with HFpEF than HFrEF. DNMT3A was the most commonly mutated gene. Patients with CHIP had higher concentrations of pro-inflammatory interleukins but CHIP was not associated with previous MI or NT-proBNP. Conclusions: There is a substantial prevalence of CHIP in patients admitted to hospital with HF. In this cohort, CHIP was uncommon in patients with HFpEF under the age of 70 years but was frequent in older patients. The association between age and CHIP was stronger in HFpEF than HFrEF. CHIP was associated with inflammation. Its potential role in the pathogenesis of HF warrants further exploration in larger groups, including in elderly patients with HFpEF.
Abstract 12101: Impact of COVID-19 Pandemic on the Incidences of Hospitalizations for Acute Myocardial Infarction and Out-of-Hospital Cardiac Death. <i>A Nation-Level Analysis</i>
Authors: Zuzana J Motovska, Jiri Jarkovsky, Ota HLINOMAZ, Petr Kala, Milan Hromadka, Jan Mrozek, Jan Precek, Pavol Tomasov, Martin Kozel, Tamilla Muzafarova, Ondrej Sanca
Journal: Circulation (2022)

Introduction: COVID-19 infection has increased the risk of thrombosis, and the pandemic has impacted the utilization of healthcare services. Hypothesis: The study aims to investigate the consequences of the COVID-19 pandemic on the incidence of hospitalization for acute myocardial infarction (IH-AMI) and out-of-hospital cardiovascular deaths rate (OH-CVD). Methods: The analysis was done on data collected in the National Database of Death Records, the National Health Information System, and the Information System of Infectious Diseases. Incidence and number of deaths were expressed per 100 000 inhabitants. For comparison of time periods incidence rate ratio was applied. Over-mortality was described as a change in % against the reference period 2016-2019. Results: The population for the analysis consisted of 50,745 AMI cases and 204,392 OH-deaths from any cause. In the pandemic year (vs. 2016-2019 period), there was a significant decrease in AMI hospitalizations with an incidence rate ratio of 0.949 (0.911;0.989) for acute STEMI and 0.949 (0.911;0.989) for NSTEMI, respectively. A significant relationship was found between the decrease in acute STEMI hospitalizations and the number of COVID-infected patients. The risk of OH-CVD increased significantly in 2020 compared to the mean death rates in 2016-2019. The analysis of over-mortality against the reference period 2016-2019 shows the increase of OH-CVD associated with the decrease in hospitalization for acute STEMI significantly related to the number of COVID19 cases (Figure). Conclusions: The COVID-19 pandemic significantly affected the number of IH-AMI while increasing the incidence of OH-CVD. These changes were directly impacted by the number of infected in the population. It is, therefore, necessary to focus efforts on informing the population about the safety of hospitalization and ensuring full availability of health care services even in pandemic times.
Abstract 11215: Comparative Effectiveness of Alcohol Septal Ablation versus Septal Myectomy on Mortality in Patients With Hypertrophic Cardiomyopathy
Authors: Itsuki Osawa, Yanling Zhao, Tadahiro Goto, Kohei Hasegawa, Mathew S Maurer, Albree Tower Rader, Michael Fifer, Muredach P Reilly, Hiroo Takayama, Yuichi J Shimada
Journal: Circulation (2022)

Introduction: Alcohol septal ablation (ASA) and septal myectomy (SM) are two options of septal reduction therapy (SRT) for patients with medication-resistant symptomatic obstructive hypertrophic cardiomyopathy (HCM). The 2020 AHA/ACC HCM Guideline recommends SM as the first-line choice and ASA as the second-line option to be conducted only if SM is contraindicated or surgical risk is high. However, little is known about the effectiveness of ASA versus SM for HCM on mortality in the real-world settings. Objective: To compare mortality between patients with HCM who underwent ASA and those who had SM using population-based databases. Methods: We identified patients with HCM who underwent an SRT from 2007 through 2014 using the SPARC database — a comprehensive, all-payer claims database that includes record of every inpatient stay and outpatient visit in New York State. We compared mortality at 15, 30, 180, and 360 days after SRT between the ASA group and the SM group (the reference group) using unadjusted analysis, propensity score matching (PSM), and inverse probability weighting (IPW). In the PSM and IPW models, we adjusted for age, sex, race/ethnicity, insurance type, and each item in the Elixhauser Comorbidity Index. Results: We identified 755 patients with HCM who underwent an SRT, including 348 in the ASA group and 407 in the SM group. In the unadjusted analysis, mortality in the ASA group was lower than that in the SM group (crude mortality at 360 days, 3.7% vs. 7.4%; Figure ). Using the PSM method, mortality was lower in the ASA group in the 180-day and 360-day post-SRT periods (adjusted odds ratio [aOR] = 0.31 at 360 days; 95% confidence interval [CI], 0.09-0.93; P = 0.049). The IPW model showed consistent findings with the PSM model (aOR = 0.44 at 360 days; 95% CI, 0.21-0.88; P = 0.02). Conclusions: Patients with HCM who underwent ASA had lower mortality than those who had SM during a 1-year post-SRT period in this population-based study.
Abstract 11489: Pregnancy Increases Cardiac Vulnerability to Post-Partum Pathological Stimuli
Authors: Yijun Yang, Justin Kurian, Jaslyn Johnson, Hajime KUBO, Remus M Berretta, Mohsin Khan, Sadia Mohsin, Steven R Houser
Journal: Circulation (2022)

Introduction: The hemodynamic demands on the heart during normal pregnancy induce physiological cardiac hypertrophy. Together with exercise induced cardiac hypertrophy and cardiac enlargement during post-natal growth, these physiological cardiac adaptations are distinct from pathological hypertrophy caused by heart diseases including volume/pressure overload. Exercise-induced cardiac hypertrophy can induce a protective phenotype that leads to resistance from ischemic injury or pressure overload induced pathological remodeling. Whether pregnancy induced cardiac hypertrophy can also protect the heart from post-partum (PP) pathological stimuli remains unknown and is the focus of this study. Methods: We challenged both post-partum and age matched non-pregnant female C57BL/6 mice with 7-day osmotic minipump infusion of Angiotensin II/phenylephrine (AngII/PE) and determined the cardiac alterations. Results: PP mice had more severe cardiac pathological remodeling after AngII/PE infusion compared with non-pregnant counterparts, with greater increases in heart weight, cardiomyocyte hypertrophy and fibrosis. Echocardiography showed both left and right ventricular hypertrophy without overt systolic dysfunction. PP mice had greater elevations in expression levels of fetal genes and fibrotic genes compared with non-pregnant mice after AngII/PE infusion. RNA-sequencing analysis suggested a more robust change in gene expression level in PP mice after AngII/PE treatment compared to non-pregnant counterparts, with a substantial role for extracellular matrix organization genes. We also found a significant alteration of gene expression levels for enriched extracellular structural organization at 1-day PP, which underlies ongoing structural re-organization in the myocardium shortly after deliver. These PP changes may predispose the heart to adverse remodeling when simultaneously challenged with pathological stimuli. Conclusions: Pregnancy induced cardiac remodeling does not protect the heart against PP pathological stimuli. In fact, the rapid remodeling in the PP heart may predispose it to exacerbation of pathological remodeling.
Abstract 11151: Pre-Operative Malnutrition Increases Risk of Major Infection and Death in Hospital After Ventricular Septal Defect Closure in Low-Resource Settings
Authors: Rachel E Wittenberg, Kimberlee Gauvreau, Christopher Duggan, Xinwei Du, Do Giang, VENKATA KRISHNA KISHORE JAYANTHI, Nestor Sandoval, Kathy J Jenkins
Journal: Circulation (2022)

Introduction: High energy requirements and poor feeding due to left-to-right shunting can lead to growth failure in patients with ventricular septal defect (VSD) but the effect of malnutrition on surgical outcomes is not well known, especially in low-resource settings. More data would inform decisions on whether nutritional repletion should occur pre-operatively or be deferred until after surgery. Methods: We analyzed cases of isolated VSD +/- ASD or PDA closure in children &lt; 5 years old from 19 centers in 10 low- and middle-income countries with complete audited data collected as part of the International Quality Improvement Collaborative for Congenital Heart Disease from 2016 - 2020. Premature infants and those with known genetic/non-cardiac structural anomalies were excluded. We examined inter-center variation in weight-for-height z score (WHZ) and adjusted for age and major medical illness to calculate odds ratios (OR) of death and major infection (surgical site infection or bacterial sepsis) during hospitalization for changes in WHZ, and for patients with moderate acute malnutrition (-3 &lt; WHZ ≤ -2; MAM) or severe acute malnutrition (WHZ ≤ -3; SAM) versus those without malnutrition (WHZ &gt; -2). Results: Among 6441 VSD closures (5023 membranous, 160 muscular, 73 AV canal, 1046 infundibular, 139 DORV), median age was 8 months (1 day - 4.4 years). Median WHZ at time of surgery was -1.1 (-8.0 - 7.4); 949 patients (15%) had MAM and 1026 (16%) had SAM. Median WHZ (-3.52 - 0.35) and rates of MAM (19 - 80%) and SAM (6 - 63%) varied among centers. Overall, 0.5% died in hospital and 1.2% had major post-operative infection. Odds of major infection (OR 1.07, 95% CI 0.89-1.29) and mortality (OR 1.18, 0.93-1.49) increased for each one unit decrease in WHZ. For the MAM group, odds of major infection (OR 1.50, 0.67-3.37) and mortality (OR 1.32, 0.50-3.49) were increased compared to those without malnutrition. For SAM, odds were higher, and were significant for major infection (OR 2.15, 1.01-4.56) and nearly so for mortality (OR 1.93, 0.98-3.77). Conclusions: Malnutrition is common in children undergoing VSD closure in low-resource settings and increases risk of major infection and death, especially in cases of SAM. Pre-operative nutritional repletion may be considered to reduce risk.
Abstract 12628: Evaluation of Time From Pre-Hospital Symptom Onset to Angiography on Coronary Artery Occlusion Status and Outcomes in Patients Presenting With NSTE-ACS
Authors: Sukardi Suba, Mary G Carey, Michele M Pelter
Journal: Circulation (2022)

Introduction: Current guidelines for invasive coronary angiography (ICA) in patients presenting with NSTE-ACS outline two treatment pathways: early (within 24 hours [hrs]); or late (&gt;24 hrs). Time of hospital admission is used as the start time, however, we hypothesize that pre-hospital time of symptom onset may be a more optimal starting time. This study was designed to test optimal symptom onset-to-angiography time (OAT) and its association with the presence of coronary occlusion and adverse outcomes. Methods: Secondary data analysis in NSTE-ACS patients (pre-COVID-19) who underwent ICA. We tested the optimal cutoff point of OAT in classifying coronary occlusion using Youden-index analysis. We tested the association of OAT and in-hospital complication (i.e., myocardial infarction [MI] after admission, unplanned transfer to the cardiac intensive care unit, pulmonary edema, cardiogenic shock, dysrhythmia with intervention) and hospital length of stay [LOS]) using regression models. Results: In 163 patients: 124 (76%) had an occluded artery; 37 (23%) had an in-hospital complication. Overall, the mean OAT was 26±22 hrs (24±22 vs. 31±21, with and without occluded artery, respectively), and the median LOS was 55 hrs. The Youden-index optimum OAT cutoff point was 13.4 hrs. In the two logistic models, the adjusted OAT was associated with the presence of coronary occlusion (Figure A). OAT, as a continuous variable, was associated with LOS ( β =0.64, 95% CI 0.08-1.21, p =0.025), no other in-hospital complications were significant (Figure B). Conclusions: In patients presenting with NSTE-ACS, OAT at both 13.4 and &lt;24 hrs is a significant predictor of the presence of coronary artery occlusion. Every hour of delayed OAT was associated with a prolonged hospital LOS 0.64 hrs (38 min). Symptom onset appears to be an important starting point in determining optimal timing of ICA in patients with NSTE-ACS, but requires further study with a large sample of patients.